Transport of the leaderless protein Ku on the cell surface of activated monocytes regulates their migratory abilities.

Recent evidence shows that the DNA repair protein Ku is expressed on the surface of a subset of cells, where it contributes to adhesion and invasion processes, and also to viral or bacterial entry into target cells. Here, we show that Ku was expressed on the cell surface during activation of human monocytes and that its expression was independent of the conventional endoplasmic reticulum (ER)/Golgi secretory pathway. Ku inhibition, by blocking antibodies, decreases the migration of monocytes on fibronectin and laminin. On activation, nuclear Ku seems to move to the periphery of the cell and it shows a punctuate staining in the cytoplasm. The cytoplasmic distribution of Ku was shown to be unaltered by brefeldin A. Protease protection experiments show that Ku is contained within vesicles in activated monocytes. These data support a new role for Ku in the migration of monocytes into tissues, which depends on a tightly regulated pathway of intracellular redistribution

Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer.

International audienceAmong the many different cell types surrounding breast cancer cells, the most abundant are those that compose mammary adipose tissue, mainly mature adipocytes and progenitors. New accumulating recent evidences bring the tumor-surrounding adipose tissue into the light as a key component of breast cancer progression. The purpose of this review is to emphasize the role that adipose tissue might play by locally affecting breast cancer cell behavior and subsequent clinical consequences arising from this dialog. Two particular clinical aspects are addressed: obesity that was identified as an independent negative prognostic factor in breast cancer and the oncological safety of autologous fat transfer used in reconstructive surgery for breast cancer patients. This is preceded by the overall description of adipose tissue composition and function with special emphasis on the specificity of adipose depots and the species differences, key experimental aspects that need to be taken in account when cancer is considered

Adipocyte Extracellular Vesicles Decrease p16INK4A in Melanoma: An Additional Link between Obesity and Cancer

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Structural and Functional Interaction between the Human DNA Repair Proteins DNA Ligase IV and XRCC4▿ †

Nonhomologous end-joining represents the major pathway used by human cells to repair DNA double-strand breaks. It relies on the XRCC4/DNA ligase IV complex to reseal DNA strands. Here we report the high-resolution crystal structure of human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV. The structure differs from the homologous Saccharomyces cerevisiae complex and reveals an extensive DNA ligase IV binding interface formed by a helix-loop-helix structure within the inter-BRCT linker region, as well as significant interactions involving the second BRCT domain, which induces a kink in the tail region of XRCC4. We further demonstrate that interaction with the second BRCT domain of DNA ligase IV is necessary for stable binding to XRCC4 in cells, as well as to achieve efficient dominant-negative effects resulting in radiosensitization after ectopic overexpression of DNA ligase IV fragments in human fibroblasts. Together our findings provide unanticipated insight for understanding the physical and functional architecture of the nonhomologous end-joining ligation complex